rs142894245

Variant names:

• chr9-119208818-G-A
• rs142894245
• NM_014618.3:c.1046C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-119208818-G-A
• chr9-119208818-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_014618.3(BRINP1):​c.1046C>T​(p.Thr349Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,614,190 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (15 hom.)
• Consequence: BRINP1 NM_014618.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.16
• Publications: 5 publications found

Genes affected

BRINP1 (HGNC:2687): (BMP/retinoic acid inducible neural specific 1) This gene is located within a chromosomal region that shows loss of heterozygosity in some bladder cancers. It contains a 5' CpG island that may be a frequent target of hypermethylation, and it may undergo hypermethylation-based silencing in some bladder cancers. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0053915083).
• BP6: Variant 9-119208818-G-A is Benign according to our data. Variant chr9-119208818-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 730457.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 268 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014618.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRINP1	NM_014618.3	MANE Select	c.1046C>T	p.Thr349Met	missense	Exon 7 of 8	NP_055433.2	O60477-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRINP1	ENST00000265922.8	TSL:1 MANE Select	c.1046C>T	p.Thr349Met	missense	Exon 7 of 8	ENSP00000265922.2	O60477-1
	BRINP1	ENST00000958983.1		c.1046C>T	p.Thr349Met	missense	Exon 7 of 8	ENSP00000629042.1
	BRINP1	ENST00000936749.1		c.839C>T	p.Thr280Met	missense	Exon 7 of 8	ENSP00000606808.1

Frequencies

GnomAD3 genomes AF: 0.00176 AC: 268 AN: 152210 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00706

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00200

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.00214 AC: 537 AN: 251278 AF XY: 0.00217

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00702

Gnomad NFE exome AF: 0.00199

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00210 AC: 3072 AN: 1461862 Hom.: 15 Cov.: 32 AF XY: 0.00208 AC XY: 1515 AN XY: 727226

African (AFR) AF: 0.000239 AC: 8 AN: 33480

American (AMR) AF: 0.00130 AC: 58 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00321 AC: 277 AN: 86254

European-Finnish (FIN) AF: 0.00582 AC: 311 AN: 53416

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.00207 AC: 2303 AN: 1112002

Other (OTH) AF: 0.00189 AC: 114 AN: 60394

GnomAD4 genome AF: 0.00176 AC: 268 AN: 152328 Hom.: 3 Cov.: 32 AF XY: 0.00199 AC XY: 148 AN XY: 74480

African (AFR) AF: 0.000265 AC: 11 AN: 41578

American (AMR) AF: 0.00190 AC: 29 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4826

European-Finnish (FIN) AF: 0.00706 AC: 75 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00200 AC: 136 AN: 68036

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00172 Hom.: 1

Bravo AF: 0.00136

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00256 AC: 22

ExAC AF: 0.00208 AC: 252

Asia WGS AF: 0.00202 AC: 7 AN: 3476

EpiCase AF: 0.00196

EpiControl AF: 0.00160

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.2
DANN	Benign	0.18
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.0054	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.58	N
PhyloP100		1.2
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.51	N
REVEL	Benign	0.017
Sift	Benign	1.0	T
Sift4G	Benign	0.35	T
Polyphen		0.0030	B
Vest4		0.16
MVP		0.093
MPC		0.46
ClinPred		0.0011	T
GERP RS		-0.89
Varity_R		0.016
gMVP		0.29
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs142894245; hg19: chr9-121971096;